Role of heart fatty acid binding protein in early detection of non ST-elevation myocardial infarct and its comparison with other cardiac markers
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RESEARCH ARTICLE
Role of heart fatty acid binding protein in early detection of non ST-elevation
myocardial infarct and its comparison with other cardiac markers
Syed Muhammad Salman Habib,1 Abdul Rasheed Khan,2 Sultana Habib,3 Syed Zia Ullah,4 Riffat Sultana,5 Qazi Daniyal Tariq,6
M. Aslam Zardari,7 Atiya Imdad8
Abstract
Objectives: To determine the role of heart fatty acid-binding protein in early detection of non-ST-elevation
myocardial infarction and its comparison with two other cardiac markers.
Methods: The cross-sectional study was conducted at Abbasi Shaheed Hospital, Karachi, from June 2012 to June
2014, and comprised patients presenting at the emergency department within two hours of chest pain and who
were subsequently referred to the cardiology department with a provisional diagnosis of either unstable angina or
non-ST-elevation myocardial infarction. Relevant history was taken on a specific proforma and electrocardiogram
as well as routine investigations were done in the emergency department. Blood samples from the subjects were
tested for the diagnosis of myocardial infarction through detection of heart fatty acid-binding protein, Troponin-I
and Creatine kinase-myocardial band. Sensitivity and specificity of the three markers were calculated keeping
coronary angiography as the gold standard. Data was analysed using SPSS 17.
Results: Out of 250 patients, 153(61.2%) were males. The overall mean age was 54.45±13.92 years. Sensitivity and
specificity of heart fatty acid-binding protein were 80.6% and 78.5% (p0.05), and for Creatine Kinase-myocardial band, 29.5% and 67.8% (p>0.05).
Conclusion: Heart fatty acid-binding protein was found to be a good diagnostic tool for the detection of non-ST-
elevation myocardial infarction.
Keywords: Non ST-elevation myocardial infarct, Cardiac markers, Heart fatty acid-binding protein, Troponin-I,
Creatine kinase isoenzyme MB, Angiography. (JPMA 71: 233; 2021)
DOI: https://doi.org/10.47391/JPMA.270
Introduction Acute coronary syndrome (ACS) encompasses a spectrum
Cardiovascular disease (CVD) is estimated to be the of CAD, including unstable angina (UA), non-ST-elevation
number one cause of death worldwide. Among other myocardial infarction (NSTEMI) and ST-elevation
causes, coronary artery disease (CAD) is supposed to be myocardial infarction (STEMI).5 Studies have shown that
the most fatal and prevalent manifestation of CVD. CVD is patients with NSTEMI constitute the majority (54%) of
expected to be affecting more than 23 million people acute myocardial infarction (AMI) in-patients. A diagnosis
annually by 2030.1,2 Although chest pain can be a of ACS usually needs significant ST-T changes in
manifestation of non-cardiac disease, cardiac chest pain electrocardiogram (ECG) and/or increased levels of
alone constitutes 50% of all cases presenting with chest myocardial disease markers in plasma. The absence of
pain.3 Chest pain of cardiac origin usually needs such changes, however, is not enough to exclude ACS,
aggressive management and monitoring in order to and it makes ACS diagnosis difficult to make in its early
prevent sudden cardiac death, which is the most dreadful phase. Early diagnosis, however, is essential and early risk
manifestation of CAD.4 stratification is important to ensure the accurate, timely
and cost-effective management of non-ST elevation acute
coronary syndrome (NSTE-ACS) patients.6 In order to
1Department of Nuclear Medicine, Karachi Institute of Radiotherapy Nuclear assess patients with confirmed ACS diagnosis, several
Medicine, Karachi, 2Department of Cardiology, Abbasi Shaheed Hospital and scoring methods can be used, including the Platelet
Karachi Institute of Heart Disease, Karachi, 3,5Department of Cardiology, Glycoprotein IIb/IIIa in Unstable Angina: Receptor
Karachi Institute of Heart Disease, Karachi 4,7Department of Adult Cardiology, Suppression Using Integrilin Therapy (PURSUIT),
National Institute of Cardiovascular Diseases, Karachi, Pakistan, 6MBBS Thrombolysis in Myocardial Infarction (TIMI) and Global
Student, New York, America, 8Department of Cardiology, Abbasi Shaheed Registry of Acute Coronary Events (GRACE) scores.7
Hospital, Karachi, Pakistan.
Correspondence: Syed Muhammad Salman Habib. The current study was planned to determine the early
Email: salmanhabib75@hotmail.com diagnostic role of heart fatty acid-binding protein (H-
Vol. 71, No. 1-B, January 2021
S. M. S. Habib, A. R. Khan, S. Habib, et al
234
FABP) in NSTEMI compared to the role of like cardiac 13.9±1.08 IU/L and the study protocol required all cardiac
troponin (cTn-I) and creatine kinase-myocardial band (CK- biomarkers to be tested within 2 hours of onset of chest
MB). pain.
Patients and Methods Coronary angiogram was performed using standard
The cross-sectional study was conducted at Abbasi techniques as per hospital protocol and data was
Shaheed Hospital, Karachi, from June 2012 to June 2014. recorded by follow-up of patients either through direct
After approval from the institutional ethics committee, contact with patients or through indirectly-collected
the sample size was calculated using epitool online angiogram results from the referred hospital. Significant
sample size calculator81 for sensitivity and specificity CAD was defined as a lesion with >50% stenosis of the left
employing the reported diagnostic accuracy of cardiac main (LM) artery or >70%stenosis in any major coronary
biomarkers8 at 95% confidence level and 80% power. The artery or its branches.
sample was inflated to avoid underpowered analysis. Data were organized on Microsoft Excel 2007 and was
Those included were subjects of either gender aged >25 analysed using SPSS 17. Continuous variables were
years presenting at the emergency department (ED) presented as mean ± standard deviation and categorical
within two hours of the onset of chest pain lasting for >20 variables as frequencies and percentages. Sensitivity and
minutes suspected of having NSTE-ACS. Those excluded specificity of the cardiac biomarkers were calculated and
were case having recently been diagnosed STEMI or all parameters were analysed using cross-tabulation,
percutaneous coronary intervention (PCI) / coronary while significant differences were assessed using chi-
artery bypass grafting (CABG) within the preceding 30 squared test. P1.5 mg/dl significant.
or any known renal disease, and non-ACS patients.
Results
All patients were enrolled after obtaining informed Of the 250 subjects, 153(61.2%) were males. The overall
consent. Any patient with a working diagnosis of ACS was mean age was 54.45±13.92 years. The most common age
registered initially and several CAD determinants, like range was 35-44 years (Figure-1). On admission,
onset and duration of chest pain, quality of pain, risk 194(77.6%) patients had typical chest pain and 101(52%)
factors and history of CAD, were noted. Blood sample was had chest heaviness with or without pain radiating to the
taken and tested for H-FABP, Troponin-I (Trop-I) and CK- left shoulder. Presented symptoms were sweating in
MB irrespective of the ECG findings and clinical history. 22(11.3%) patients, palpitation 41(21.1%), nausea 9(4.6%),
Data was collected based on positive biomarker results, vomiting 4(2%) and dyspnoea 17(8.7%). Also, 25(10%)
meaning any of the 3 biomarkers within two hours patients, specifically diabetics, presented with atypical
interval after onset of chest pain diagnosed as NSTEMI, chest pain like epigastric pain or/and right shoulder pain,
and negative biomarker result within 2 hours' time and 31(12.4%) presented with dyspnoea.
interval after onset of chest pain was labelled as unstable
angina (UA). After giving initial Hypercholesterolaemia was the most common risk factor
management, all patients were referred
for coronary angiography.
Qualitative determination of H-FABP
was done using rapid chromatographic
immunoassay Cardio-Detect kit with a
cut-off value of 7.0ng/ml which is a
visual-based qualitative test. To assess
serum qualitative level of Trop-I,
immune-chromatographic qualitative
Cardiac-I Kit with a cutoff value of 0.5
ng/mL was used. Heparinised plasma
samples were drawn for CK-MB and
quantitative analysis was done using
spectrophotometer method on a semi-
automated analyser (Photometer).
Normal mean CK-MB level was taken as Figure-1: Age distribution of the study population.
J Pak Med Assoc235 Role of heart fatty acid binding protein in early detection of non ST-elevation myocardial infarct...
biomarkers. A study11 using qualitative
H-FABP as a diagnostic marker of cardiac
disease within the first six hours in
patients with STEMI reported the
sensitivity of H-FABP as 95% in
comparison with Trop-I (76%) and CK-MB
(38%). In the current study, H-FABP
assessment within two hours revealed 19
false-positive (FP) and 6 false-negative
(FN) patients. FP result of H-FABP mostly
developed in patients who had renal
impairment during admission in the
coronary care unit (CCU). Naroo et al.12
also showed that renal failure could
result in FP H-FABP levels. Literature has
also reported that H-FABP could be
regarded as a sensitive marker for minor
myocardial injury with ischaemia but no
detectable levels of standard cardiac
Figure-2: Diagnostic accuracy of heart fatty acid-binding protein (H-FABP), Troponin-I and Creatine kinase biomarkers in the blood.13 This could
isoenzymes M and B (CK-MB) in < 2 hours after onset of chest pain using coronary angiography as gold standard. also be a reason for FP findings in
ischaemic patients with UA that could
not have been detected by our reference
106(42.4%) followed by hypertension (HTN) 103(41.2%), standard Trop-I, and we labelled these results as FP due to
smoking 86(34.4%) and diabetes 73(29.2%). Further, our standard settings. The results for FN were also
53(21.2%) patients were obese and 50(20%) had a reviewed to find the reason, but no precise reason was
positive family CAD history. found except that relatively high number of early
presenters within an hour after the onset of symptoms
Overall, 85(34%) patients were diagnosed as NSTEMI, may be the factor for FN results which was comparable
while 165(66%) were UA. True-positive (TP) and true- with the outcome of Willemsen et al. who also included
negative (TN) values for all the three cardiac biomarkers early presenters in their study.14 Trop-I assessment within
were assessed (Figure-2). Using coronary angiogram as two hours revealed 61 FP and 7 FN patients. The reason
the gold standard, the sensitivity and specificity of for FP elevation of troponin was the existence of fibrin in
sensitivity and specificity of H-FABP were 80.6% and the specimens or development of endogenous
78.5% (pS. M. S. Habib, A. R. Khan, S. Habib, et al
236
found due to the presence of unbound component of small proteins that enable H-FABP to exhibit an early and
troponin in the cardiac myocytes, which is about 6% of significant release after myocardial injury and make it
cTnT and 3% of cTnI, but CK-MB levels remained in the more easily being detected.
reference range. Similar findings were reported by
Tanindi et al.15 We observed FP result of CK-MB in a In terms of limitations the study comprised hospital-
fraction of patients presenting with hypertensive crisis based referral population which is fairly representative of
along with neurological ischaemia or stroke. Although an ED setting and may not necessarily reproduce results
this scenario can point towards a diagnosis of ACS, but for the general population. Also, owing to the limited
normal troponin along with elevated CK-MB suggests that numbers of H-FABP kits, we could not compare H-FABP
the surge in CK-MB is non-cardiac in origin which is with other biomarkers in the late time period > 2 hours.
common in patients with ischaemic stroke. Ay et al,17 also Conclusion
reported similar findings.
H-FABP was found to be a better diagnostic tool in NSTE-
The demographic data of the current study showed mean ACS, especially in the early time period window, after
age of 54.20±13.86 years while one study done in chest pain. As an early marker, it can reliably diagnose
Pakistan reported 60±5.0 years in their population.18 The ACS. Compared to cardiac troponin, H-FABP is emerging
reason for younger age in our population may due to the as a diagnostic marker to rule out non-AMI patients in the
fact that most patients had at least three or more co- early acute phase.
morbids. We also found the male gender to be more
Disclaimer: The text is based on an MD thesis.
prone to CAD, which has also been reported earlier.19,20 It
is also postulated in literature that young and female Conflict of Interest: None.
gender imply lower CAD risk due to oestrogen's
protective effects. This might be a reason that most Source of Funding: H-FABP Kits (CardioDetect) were
women with clinical CAD are generally older than men.21 provided by Maple Pharmaceuticals, Karachi.
One study22 also reported that young women who by References
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Stroke Is Not Cardiac in Origin: Comparison with Troponin T
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